scholarly journals A brain structural connectivity biomarker for diagnosis of autism spectrum disorder in early childhood

2021 ◽  
Author(s):  
Xi Jiang ◽  
Xiao-Jing Shou ◽  
Zhongbo Zhao ◽  
Fanchao Meng ◽  
Jiao Le ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Cognitive Development ◽  
Symptom Severity ◽  
Structural Connectivity ◽  
Autism Spectrum ◽  
Social Recognition ◽  
Spectrum Disorder ◽  
Connection Matrix ◽  
Independent Validation ◽  
Discovery Dataset

Objective: Autism spectrum disorder (ASD) is associated with altered brain development, but it is unclear which specific structural changes may serve as potential diagnostic markers. This study aimed to identify and model brain-wide differences in structural connectivity using MRI diffusion tensor imaging (DTI) in young ASD and typically developing (TD) children (3.5-6 years old). Methods: Ninety-three ASD and 26 TD children were included in a discovery dataset and 12 ASD and 9 TD children from different sites included as independent validation datasets. Brain-wide (294 regions) structural connectivity was measured using DTI (fractional anisotropy, FA) under sedation together with symptom severity and behavioral and cognitive development. A connection matrix was constructed for each child for comparisons between ASD and TD groups. Pattern classification was performed and the resulting model tested on two independent datasets. Results: Thirty-three structural connections showed increased FA in ASD compared to TD children and associated with both symptom severity and general cognitive development. The majority (29/33) involved the frontal lobe and comprised five different networks with functional relevance to default mode, motor control, social recognition, language and reward. Overall, classification accuracy is very high in the discovery dataset 96.77%, and 91.67% and 88.89% in the two independent validation datasets. Conclusions: Identified structural connectivity differences primarily involving the frontal cortex can very accurately distinguish individual ASD from TD children and may therefore represent a robust early brain biomarker.

scholarly journals Cariprazine alleviates core behavioral deficits in the prenatal valproic acid exposure model of autism spectrum disorder

2021 ◽  
Author(s):  
Viktor Román ◽  
Nika Adham ◽  
Andrew G. Foley ◽  
Lynsey Hanratty ◽  
Bence Farkas ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Social Communication ◽  
Partial Agonist ◽  
Social Play ◽  
Autism Spectrum ◽  
Social Recognition ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Exposure Model ◽  
Behavioral Deficits

Abstract Rationale Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and interaction and restricted, repetitive behaviors. The unmet medical need in ASD is considerable since there is no approved pharmacotherapy for the treatment of these deficits in social communication, interaction, and behavior. Cariprazine, a dopamine D3-preferring D3/D2 receptor partial agonist, is already approved for the treatment of schizophrenia and bipolar I disorder in adults; investigation in patients with ASD is warranted. Objectives The aim of this study was to investigate the effects of cariprazine, compared with risperidone and aripiprazole, in the rat prenatal valporic acid (VPA) exposure model on behavioral endpoints representing the core and associated symptoms of ASD. Methods To induce the ASD model, time-mated Wistar rat dams were treated with VPA during pregnancy. Male offspring were assigned to groups and studied in a behavioral test battery at different ages, employing social play, open field, social approach-avoidance, and social recognition memory tests. Animals were dosed orally, once a day for 8 days, with test compounds (cariprazine, risperidone, aripiprazole) or vehicle before behavioral assessment. Results Cariprazine showed dose-dependent efficacy on all behavioral endpoints. In the social play paradigm, only cariprazine was effective. On the remaining behavioral endpoints, including the reversal of hyperactivity, risperidone and aripiprazole displayed similar efficacy to cariprazine. Conclusions In the present study, cariprazine effectively reversed core behavioral deficits and hyperactivity present in juvenile and young adult autistic-like rats. These findings indicate that cariprazine may be useful in the treatment of ASD symptoms.

scholarly journals Decreased homotopic interhemispheric functional connectivity in children with autism spectrum disorder

2020 ◽  
Author(s):  
Shuxia Yao ◽  
Menghan Zhou ◽  
Yuan Zhang ◽  
Feng Zhou ◽  
Qianqian Zhang ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Functional Connectivity ◽  
Symptom Severity ◽  
Visual Processing ◽  
Brain Networks ◽  
Cingulate Cortex ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Volume Changes ◽  
Processing Network

AbstractWhile a number of functional and structural changes occur in large-scale brain networks in autism spectrum disorder (ASD), reduced interhemispheric resting state functional connectivity (rsFC) between homotopic regions may be of particular importance as a biomarker. ASD is an early-onset developmental disorder and neural alterations are often age-dependent, reflecting dysregulated developmental trajectories, although no studies have investigated whether homotopic interhemispheric rsFC alterations occur in ASD children. The present study conducted a voxel-based homotopic interhemispheric rsFC analysis in 146 SD and 175 typically developing children under age 10 and examined associations with symptom severity in the Autism Brain Imaging Data Exchange datasets. Given the role of corpus callosum (CC) in interhemispheric connectivity and reported CC volume changes in ASD we additionally examined whether there were parallel volumetric changes in ASD children. Results demonstrated decreased homotopic rsFC in ASD children in the medial prefrontal cortex, precuneus and posterior cingulate cortex of the default mode network (DMN), the dorsal anterior cingulate cortex of the salience network, the precentral gyrus and inferior parietal lobule of the mirror neuron system, the lingual, fusiform and inferior occipital gyri of the visual processing network and thalamus. Symptom severity was associated with homotopic rsFC in regions in the DMN and visual processing network. There were no significant CC volume changes in ASD children. The present study shows that reduced homotopic interhemispheric rsFC in brain networks in ASD adults/adolescents is already present in children of 5-10 years old and further supports their potential use as a general ASD biomarker.

scholarly journals A Temporal Activity of CA1 Neurons Underlying Short-Term Memory for Social Recognition Altered in PTEN Mouse Models of Autism Spectrum Disorder

2021 ◽  
Vol 15 ◽  
Author(s):  
An-Ping Chai ◽  
Xue-Feng Chen ◽  
Xiao-Shan Xu ◽  
Na Zhang ◽  
Meng Li ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Short Term Memory ◽  
Autism Spectrum ◽  
Social Recognition ◽  
Neuronal Firing ◽  
Spectrum Disorder ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Ca1 Neurons

Memory-guided social recognition identifies someone from previous encounters or experiences, but the mechanisms of social memory remain unclear. Here, we find that a short-term memory from experiencing a stranger mouse lasting under 30 min interval is essential for subsequent social recognition in mice, but that interval prolonged to hours by replacing the stranger mouse with a familiar littermate. Optogenetic silencing of dorsal CA1 neuronal activity during trials or inter-trial intervals disrupted short-term memory-guided social recognition, without affecting the ability of being sociable or long-term memory-guided social recognition. Postnatal knockdown or knockout of autism spectrum disorder (ASD)-associated phosphatase and tensin homolog (PTEN) gene in dorsal hippocampal CA1 similarly impaired neuronal firing rate in vitro and altered firing pattern during social recognition. These PTEN mice showed deficits in social recognition with stranger mouse rather than littermate and exhibited impairment in T-maze spontaneous alternation task for testing short-term spatial memory. Thus, we suggest that a temporal activity of dorsal CA1 neurons may underlie formation of short-term memory to be critical for organizing subsequent social recognition but that is possibly disrupted in ASD.

Development of Lying and Cognitive Abilities

2018 ◽  
pp. 398-407
Author(s):  
Victoria Talwar
Keyword(s):  
Autism Spectrum Disorder ◽  
Cognitive Development ◽  
Theory Of Mind ◽  
Executive Functioning ◽  
Cognitive Functions ◽  
Cognitive Abilities ◽  
Autism Spectrum ◽  
Spectrum Disorder

The emergence and development of children’s lie-telling is closely associated with their developing cognitive abilities. Telling a lie involves complicated cognitive functions including theory-of-mind understanding and executive functioning abilities. Recent research has found that lie-telling emerges in the preschool years and children’s abilities to maintain their lies improves with age. The current chapter reviews existing literature on the development of children’s lie-telling behavior and its relation to various aspects of children’s cognitive development. It covers the work of Lewis, Stanger, and Sullivan (1989), including the well-known guessing-game experiment, where the child is left alone with temptation and the instruction not to peek. Much of Talwar, Lee, et al.’s research into three-to-seven-year-old children’s lie-telling behavior is covered; and the interaction between these studies and Theory of Mind is emphasized; this is illuminated in the account of research using child subjects with Autism Spectrum Disorder.

scholarly journals Age of First Walking and Associations with Symptom Severity in Children with Suspected or Diagnosed Autism Spectrum Disorder

2019 ◽  
Vol 50 (9) ◽  
pp. 3216-3232 ◽  
Author(s):  
Lise Reindal ◽  
Terje Nærland ◽  
Bernhard Weidle ◽  
Stian Lydersen ◽  
Ole A. Andreassen ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Symptom Severity ◽  
Autism Spectrum ◽  
Spectrum Disorder

Gastrointestinal problems are associated with increased repetitive behaviors but not social communication difficulties in young children with autism spectrum disorders

Autism ◽  
2020 ◽  
pp. 136236132095950
Author(s):  
Payal Chakraborty ◽  
Kimberly L H Carpenter ◽  
Samantha Major ◽  
Megan Deaver ◽  
Saritha Vermeer ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Symptom Severity ◽  
Gastrointestinal Symptom ◽  
Gastrointestinal Symptoms ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Behavioral Symptoms ◽  
Behavioral Symptom ◽  
Communication Difficulties

Individuals with autism spectrum disorder are more likely than typically developing individuals to experience a range of gastrointestinal abnormalities, including chronic diarrhea, constipation, food sensitivities, and abdominal pain. These gastrointestinal symptoms have been associated with higher levels of irritability and aggressive behavior, but less is known about their relationship with core autism spectrum disorder symptoms. We investigated the relationship between autism spectrum disorder and gastrointestinal symptom severity while accounting for three associated behavioral symptom domains (Irritability, Aggressiveness, and Specific Fears), in a sample of 176 children (140 males and 36 females) ages 2–7 years old with autism spectrum disorder. Most participants had at least one reported gastrointestinal symptom (93.2%) and had more than one gastrointestinal symptom (88.1%). After accounting for each associated behavioral symptom domain, repetitive behaviors and stereotypies were positively associated with gastrointestinal symptom severity. Social and communication difficulties were not significantly associated with gastrointestinal symptom severity after accounting for associated behavioral symptoms. Our findings replicate a previously described association between irritability and aggression and gastrointestinal symptoms. Furthermore, gastrointestinal symptom severity is associated with repetitive behaviors, a subset of core autism spectrum disorder symptoms. This suggests that gastrointestinal symptoms may exacerbate repetitive behaviors, or vice versa, independent from other associated behavioral symptoms. Lay Abstract Individuals with autism spectrum disorder are more likely than typically developing individuals to experience a range of gastrointestinal abnormalities, including chronic diarrhea, constipation, food sensitivities, and abdominal pain. These gastrointestinal symptoms have been associated with higher levels of irritability and aggressive behavior, but less is known about their relationship with core autism spectrum disorder symptoms. We investigated the relationship between autism spectrum disorder symptom severity and gastrointestinal symptoms while accounting for three associated behavioral symptom domains (Irritability, Aggressiveness, and Specific Fears), in a sample of 176 children (140 males and 36 females) ages 2–7 years old with autism spectrum disorder. A large majority (93.2%) of the sample had at least one reported gastrointestinal symptom, and most (88.1%) participants had more than one gastrointestinal symptom. Various types of gastrointestinal symptoms were reported; the most common symptoms reported were constipation, food limits, gas/bloating, and stomach pain. After accounting for each associated behavioral symptom domain, repetitive behaviors and stereotypies were significantly associated with gastrointestinal symptom severity. Increased severity of autism spectrum disorder symptoms was correlated with increased gastrointestinal symptom severity. Social and communication difficulties were not significantly associated with gastrointestinal symptom severity after accounting for associated behavioral symptoms. Our findings replicate a previously described association between irritability and aggression and gastrointestinal symptoms. Furthermore, we found that repetitive behaviors, but not social or communication symptoms, are associated with gastrointestinal symptom severity, even after accounting for associated behavioral symptoms. This suggests that gastrointestinal symptoms may exacerbate repetitive behaviors, or vice versa, independent from other associated behavioral symptoms.

scholarly journals Distinct neural bases of disruptive behavior and autism symptom severity in boys with autism spectrum disorder

2017 ◽  
Vol 9 (1) ◽  
Author(s):  
Y. J. Daniel Yang ◽  
Denis G. Sukhodolsky ◽  
Jiedi Lei ◽  
Eran Dayan ◽  
Kevin A. Pelphrey ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Disruptive Behavior ◽  
Symptom Severity ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Neural Bases
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